Archaeological evidence of resource utilisation of the great whales over the past two millennia: A systematic review protocol.

Archaeological faunal remains provide key insights into human societies in the past, alongside information on previous resource utilisation and exploitation of wildlife populations. The great whales (Mysticete and sperm whales) were hunted unsustainably throughout the 16th - 20th centuries (herein defined as the modern period) leading to large population declines and variable recovery patterns among species. Humans have utilised whales as a resource through carcass scavenging for millennia; however, increasing local and regional ethnographic and archaeological evidence suggests that, prior to the modern period, hunting of the great whales was more common than previously thought; impacts of earlier hunting pressures on the population ecology of many whale species remains relatively unknown. Hunting guided by traditional ecological knowledge may have been sustainable and likely originated in societies that also incorporated opportunistic use of stranded individuals. The collation of georeferenced zooarchaeological data of the great whales between the 1st - 20th centuries CE worldwide will provide insight into the timescale and distribution of resource utilisation of the great whales and how this varied within and between societies, and may have changed over time. By comparing regions of known resource utilisation and breeding and feeding grounds of current-day whale populations, this information will subsequently be used to infer regions where whale populations were possibly lost or extirpated prior to detailed historical records. This systematic review protocol also provides a template for archaeologists, ecologists, and historians interested in using faunal remains to infer historical ecology and resource use of wild animal populations. The transparency of our data collection approach provides opportunities for reproducibility and comparability with future datasets.

Bone Mineral Density Response to Long-Term Bisphosphonate Treatment and Discontinuation in a Real-World Clinical Service.

OBJECTIVE: Bisphosphonate treatment does not increase bone mineral density (BMD) in all subjects particularly at the femoral neck (FN). Our aim was to evaluate the relationship between response to oral bisphosphonate (oBP) at the FN and change in BMD following discontinuation. METHODS: Data were collected retrospectively from postmenopausal women on oBP for ≥3 years, attending a real-world metabolic clinic at initiation of oBP, discontinuation, and 1 to 2 years post discontinuation. Improvement in BMD ≥4% in the FN and ≥5% for the lumbar spine (LS) were deemed clinically meaningful and used as least significant change (LSC) values. We divided subjects based on FN BMD response and compared outcomes between responders and non-responders after oBP discontinuation. RESULTS: Of the 213 subjects, 32.1% showed an increase ≥LSC at the FN compared to 57.1% at the LS on treatment (P < .0001). FN responders had lower BMD levels at pretreatment baseline than non-responders both at the FN (0.58 vs 0.62 g/cm2; P = .003) and LS (0.76 vs 0.79 g/cm2; P = .044). Off-treatment, more subjects lost BMD ≥LSC at FN in the responder group than in the non-responder group (37.5% vs 14.2%; P < .001). BMD remained above pre-treatment levels in responders after a median follow-up of 1.52 years. CONCLUSION: BMD response at FN is suboptimal in patients on oBP and is much less common than LS response. FN responders tend to lose the accumulated bone quickly off-treatment, though BMD remains above pretreatment levels. These observations suggest that new approaches may be needed to optimize osteoporosis management in real-world patients.

Active Bystander Training: Using Standardized Patient Methodology to Teach Residents to Navigate Microaggressions in Patient Encounters.

Introduction: Studies show that physicians and medical trainees who identify as underrepresented in medicine or as women experience higher rates of microaggressions during patient encounters. We designed, implemented, and evaluated an active bystander training workshop focused on mitigating microaggressions using standardized patient (SP) methodology. Methods: Internal medicine faculty members and chief residents led the workshop. Participants included 31 PGY 1 categorical and preliminary internal medicine residents. They participated in three case simulations with SPs involving microaggressions from patients toward a member of the health care team. Prior to the case simulations, a brief presentation outlined examples of microaggressions and reviewed the behavioral response framework WAKE (work with who you are, ask questions/make direct statements, involve key people, and employ distraction techniques). After each encounter, residents debriefed with an internal medicine faculty member and discussed questions related to each scenario. Results: All 31 residents participated in the workshop and, before and after the activity, completed a survey that asked them to rank their agreement with statements via a Likert scale. Participants reported statistically significant improvement in recognizing microaggressions (12% reported increase, p = .002), the ability to respond to patients who exhibit microaggressions (23% reported increase, p < .001), and the ability to debrief with team members (20% reported increase, p < .001). Discussion: SP simulations can be an effective teaching modality for microaggression response strategies during patient encounters. Additional studies are needed to further characterize the workshop's effect on other medical workforce trainees and retention of skills over time.

Peripheral Administration of Selective Glycine Transporter-2 Inhibitor, Oleoyl-D-Lysine, Reverses Chronic Neuropathic Pain but Not Acute or Inflammatory Pain in Male Mice.

Aberrations in spinal glycinergic signaling are a feature of pain chronification. Normalizing these changes by inhibiting glycine transporter (GlyT)-2 is a promising treatment strategy. However, existing GlyT2 inhibitors (e.g., ORG25543) are limited by narrow therapeutic windows and severe dose-limiting side effects, such as convulsions, and are therefore poor candidates for clinical development. Here, intraperitoneally administered oleoyl-D-lysine, a lipid-based GlyT2 inhibitor, was characterized in mouse models of acute (hot plate), inflammatory (complete Freund's adjuvant), and chronic neuropathic (chronic constriction injury) pain. Side effects were also assessed on a numerical rating score, convulsions score, for motor incoordination (rotarod), and for respiratory depression (whole body plethysmography). Oleoyl-D-lysine produced near complete antiallodynia for chronic neuropathic pain, but no antiallodynia/analgesia in inflammatory or acute pain. No side effects were seen at the peak analgesic dose, 30 mg/kg. Mild side effects were observed at the highest dose, 100 mg/kg, on the numerical rating score, but no convulsions. These results contrasted markedly with ORG25543, which reached less than 50% reduction in allodynia score only at the lethal/near-lethal dose of 50 mg/kg. At this dose, ORG25543 caused maximal side effects on the numerical rating score and severe convulsions. Oleoyl-D-lysine (30 mg/kg) did not cause any respiratory depression, a problematic side effect of opiates. These results show the safe and effective reversal of neuropathic pain in mice by oleoyl-D-lysine and provide evidence for a distinct role of glycine in chronic pain over acute or short-term pain conditions. SIGNIFICANCE STATEMENT: Partially inhibiting glycine transporter (GlyT)-2 can alleviate chronic pain by restoring lost glycinergic function. Novel lipid-based GlyT2 inhibitor ol-D-lys is safe and effective in alleviating neuropathic pain, but not inflammatory or acute pain. Clinical application of GlyT2 inhibitors may be better suited to chronic neuropathic pain over other pain aetiologies.

Glycinergic Modulation of Pain in Behavioral Animal Models.

Animal models of human pain conditions allow for detailed interrogation of known and hypothesized mechanisms of pain physiology in awake, behaving organisms. The importance of the glycinergic system for pain modulation is well known; however, manipulation of this system to treat and alleviate pain has not yet reached the sophistication required for the clinic. Here, we review the current literature on what animal behavioral studies have allowed us to elucidate about glycinergic pain modulation, and the progress toward clinical treatments so far. First, we outline the animal pain models that have been used, such as nerve injury models for neuropathic pain, chemogenic pain models for acute and inflammatory pain, and other models that mimic painful human pathologies such as diabetic neuropathy. We then discuss the genetic approaches to animal models that have identified the crucial glycinergic machinery involved in neuropathic and inflammatory pain. Specifically, two glycine receptor (GlyR) subtypes, GlyRα1(ß) and GlyRα3(ß), and the two glycine transporters (GlyT), GlyT1 and GlyT2. Finally, we review the different pharmacological approaches to manipulating the glycinergic system for pain management in animal models, such as partial vs. full agonism, reversibility, and multi-target approaches. We discuss the benefits and pitfalls of using animal models in drug development broadly, as well as the progress of glycinergic treatments from preclinical to clinical trials.

Communication skills among children with spinal muscular atrophy type 1: A parent survey.

Spinal muscular atrophy is one of the most common fatal autosomal recessive disorders. Children diagnosed with SMA Type 1 (SMAT1) demonstrate severe oral motor weakness and flaccid dysarthria progressing to complete anarthria. A review of literature illustrates that little has been described regarding augmentative and alternative communication (AAC) use among these children, although communication has a critical impact on quality of life and participation in daily activities. Responses to an investigator-developed parent survey were obtained to appraise communication skills and opportunities among children diagnosed with SMA1. Results illustrate parent perception of greater receptive than expressive language ability and highlight the benefits of implementing speech-generating devices (SGD). Barriers to SGD acquisition and implementation, including access and funding, are reported and described. Overall, families indicated that SGD increases quality of life and provides valued improvements through expanded functional communication.

Lower Limb Metaphyseal Bone Is Lost in Men with Coeliac Disease and Does Not Relate to Parathyroid Status.

Aims. To investigate regional lower limb bone density and associations with weight, PTH, and bone breakdown in coeliac men. Methods. From whole body DXA scans bone mineral density (BMD) was measured in 28 coeliac men, in the lower limb (subdivided into 6 regions, 3 being metaphyseal (mainly trabecular) and 2 diaphyseal (mainly cortical)). BMD at femoral neck (FN) and lumbar spine L2-4, body weight, height, serum calcium, alkaline phosphatase, parathyroid hormone (PTH), and urinary calcium and NTx/Cr, a measure of bone breakdown, were also measured. Age matched healthy men provided values for BMD calculation of z and T scores and for biochemical measurements. Results. Low BMD z scores were found at metaphyseal regions in the leg (p < 0.001) and in the FN (p < 0.05). The distal metaphyseal region BMD in the leg was lower than spine or FN (p < 0.05). PTH, urinary calcium/creatinine, and urinary NTx/Cr were similar to controls. Both metaphyseal and diaphyseal BMD z scores were associated with body weight (p < 0.02), but not with either PTH or urinary NTx/Cr. Conclusions. Low BMD lower limb regions comprising mostly trabecular bone occur early in CD and in the absence of elevated PTH or increased bone resorption. Low BMD is associated with low body weight.

Modality specificity and integration in working memory: Insights from visuospatial bootstrapping.

The question of how meaningful associations between verbal and spatial information might be utilized to facilitate working memory performance is potentially highly instructive for models of memory function. The present study explored how separable processing capacities within specialized domains might each contribute to this, by examining the disruptive impacts of simple verbal and spatial concurrent tasks on young adults' recall of visually presented digit sequences encountered either in a single location or within a meaningful spatial "keypad" configuration. The previously observed advantage for recall in the latter condition (the "visuospatial bootstrapping effect") consistently emerged across 3 experiments, indicating use of familiar spatial information in boosting verbal memory. The magnitude of this effect interacted with concurrent activity; articulatory suppression during encoding disrupted recall to a greater extent when digits were presented in single locations (Experiment 1), while spatial tapping during encoding had a larger impact on the keypad condition and abolished the visuospatial bootstrapping advantage (Experiment 2). When spatial tapping was performed during recall (Experiment 3), no task by display interaction was observed. Outcomes are discussed within the context of the multicomponent model of working memory, with a particular emphasis on cross-domain storage in the episodic buffer (Baddeley, 2000).

Cancer incidence in professional flight crew and air traffic control officers: disentangling the effect of occupational versus lifestyle exposures.

Flight crew are occupationally exposed to several potentially carcinogenic hazards; however, previous investigations have been hampered by lack of information on lifestyle exposures. The authors identified, through the United Kingdom Civil Aviation Authority medical records, a cohort of 16,329 flight crew and 3,165 air traffic control officers (ATCOs) and assembled data on their occupational and lifestyle exposures. Standardised incidence ratios (SIRs) were estimated to compare cancer incidence in each occupation to that of the general population; internal analyses were conducted by fitting Cox regression models. All-cancer incidence was 20-29% lower in each occupation than in the general population, mainly due to a lower incidence of smoking-related cancers [SIR (95% CI) = 0.33 (0.27-0.38) and 0.42 (0.28-0.60) for flight crew and ATCOs, respectively], consistent with their much lower prevalence of smoking. Skin melanoma rates were increased in both flight crew (SIR = 1.87; 95% CI = 1.45-2.38) and ATCOs (2.66; 1.55-4.25), with rates among the former increasing with increasing number of flight hours (p-trend = 0.02). However, internal analyses revealed no differences in skin melanoma rates between flight crew and ATCOs (hazard ratio: 0.78, 95% CI = 0.37-1.66) and identified skin that burns easily when exposed to sunlight (p = 0.001) and sunbathing to get a tan (p = 0.07) as the strongest risk predictors of skin melanoma in both occupations. The similar site-specific cancer risks between the two occupational groups argue against risks among flight crew being driven by occupation-specific exposures. The skin melanoma excess reflects sun-related behaviour rather than cosmic radiation exposure.

Matched-cohort study of body composition, physical function, and quality of life in men with idiopathic vertebral fracture.

OBJECTIVE: To determine the effect of 6 years of routine management on body composition, physical functioning, and quality of life, and their interrelationships, in men with idiopathic vertebral fracture. METHODS: Twenty men with idiopathic vertebral fracture (patients: mean ± SD age 58 ± 6 years) were age and height matched to 28 healthy controls with no known disease. The primary outcome was skeletal muscle mass (appendicular lean mass by dual x-ray absorptiometry) assessed at 2 visits (0 and 6 years). Physical functioning and quality of life domains were assessed by the Senior Fitness Test and Short Form 36 (SF-36) questionnaire at visit 2 only. Data were analyzed by repeated-measures analysis of variance, independent t-tests, and correlation. RESULTS: At visit 1, appendicular lean mass was 9% lower in patients than controls. Although patients better maintained appendicular lean mass between visits (interaction P = 0.016), at visit 2 appendicular lean mass remained 5% lower in patients than controls. Furthermore, patients' appendicular lean mass change was correlated with femoral neck bone density change (r = 0.507, P = 0.023). Physical function tests were 13-27% lower in patients compared with controls (P = 0.056 to 0.003), as were SF-36 quality of life physical domains (13-26% lower; P = 0.028 to <0.001). CONCLUSION: Despite an association between changes in muscle mass and bone density, routine management of men with idiopathic vertebral fracture does not address muscle loss. Combined with the observation of reduced physical functioning and quality of life, this study identifies novel targets for intervention in men with idiopathic vertebral fracture.

The annual incapacitation rate of commercial pilots.

INTRODUCTION: Scant data are available on the annual incapacitation rate of aircrew. This study analyzes all incapacitations occurring among UK commercial pilots, in flight and off duty, in 2004 to derive a baseline minimum annual incapacitation rate for the UK commercial pilot population. METHOD: The study cohort was all professional pilots holding a valid UK/JAR (Joint Aviation Requirements) Class 1 medical certificate and license in 2004. Three data sources were used to identify episodes of incapacitation: the statutory notification of prolonged illness, personal injury, or pregnancy to the UK Civil Aviation Authority; Mandatory Occurrence Reports (MORs) for in-flight medical incidents; and death certificates. The total number of incapacitations was expressed as a proportion of the number of professional pilots to give an incapacitation rate. RESULTS: In 2004 there were 16,145 UK/JAR professional pilot license holders. Of the notified medical events, 36 presented as incapacitations; half were cardiac or cerebrovascular. In-flight incapacitations were predominantly of psychiatric cause. There were four sudden deaths. The type of incapacitation varied with age. A male pilot in his 60s had 5 times the risk of incapacitation of a male pilot in his 40s. The annual incapacitation rate was 40/16,145 = 0.25%. DISCUSSION: Aeromedical emphasis on minimizing cardiovascular risk and monitoring the mental health of pilots remains appropriate. Age should influence the content and periodicity of regulatory aeromedical assessments. The demonstrated annual incapacitation rate of 0.25% may provide a basis for quantifying the acceptable risk for a pilot undertaking single pilot commercial air transport operations.

Cause-specific mortality in professional flight crew and air traffic control officers: findings from two UK population-based cohorts of over 20,000 subjects.

OBJECTIVE: Flight crew are exposed to several potential occupational hazards. This study compares mortality rates in UK flight crew to those in air traffic control officers (ATCOs) and the general population. METHODS: A total of 19,489 flight crew and ATCOs were identified from the UK Civil Aviation Authority medical records and followed to the end of 2006. Consented access to medical records and questionnaire data provided information on demographic, behavioral, clinical, and occupational variables. Standardized mortality ratios (SMR) were estimated for these two occupational groups using the UK general population. Adjusted mortality hazard ratios (HR) for flight crew versus ATCOs were estimated via Cox regression models. RESULTS: A total of 577 deaths occurred during follow-up. Relative to the general population, both flight crew (SMR 0.32; 95% CI 0.30, 0.35) and ATCOs (0.39; 0.32, 0.47) had lower all-cause mortality, mainly due to marked reductions in mortality from neoplasms and cardiovascular diseases, although flight crew had higher mortality from aircraft accidents (SMR 42.8; 27.9, 65.6). There were no differences in all-cause mortality (HR 0.99; 95% CI 0.79, 1.25), or in mortality from any major cause, between the two occupational groups after adjustment for health-related variables, again except for those from aircraft accidents. The latter ratios, however, declined with increasing number of hours. CONCLUSIONS: The low all-cause mortality observed in both occupational groups relative to the general population is consistent with a strong "healthy worker effect" and their low prevalence of smoking and other risk factors. Mortality among flight crew did not appear to be influenced by occupational exposures, except for a rise in mortality from aircraft accidents.

Prevalence of cardiovascular disease risk factors among UK commercial pilots.

AIM: This study is one of the largest ever completed to examine the prevalence of cardiovascular disease (CVD) risk factors among commercial aircrew. METHOD AND RESULTS: A retrospective cross-sectional study comparing prevalence of CVD risk factors age, body mass index (BMI), overweight and obesity, current smoking status, hypertension, and diabetes among commercial aircrew and the UK general population. A total of 14,379 subject records were eligible for the study. The age-sex group mean BMI was significantly lower in almost all pilot age groups compared to the general population. Overweight age-sex group prevalence was significantly higher in the <25, 35-44, 45-54, 55-64 age groups for male pilots, and lower for female pilots in the 25-34 and 45-54 age groups. Male and female pilots had significantly lower age-sex-group prevalence of obesity and current smoking compared to the general population. For hypertension, the male <25 and 35-44 year age groups had significantly higher prevalence, and the 45-54 and 55-64 year age groups had significantly lower prevalence than the general population. Age-standardised mean BMI and prevalence of overweight and hypertension were not significantly different from the highest income quintile of the general population. Age-standardised obesity and current smoking prevalence were significantly lower in pilots compared to the highest socio-economic quintile of the general population. CONCLUSION: Even when comparisons were made with the highest income quintile of the general population to control for socio-economic status, pilots had a significantly lower prevalence of obesity and smoking. This finding is consistent with a strong 'healthy worker effect'.

Application of a cardiovascular disease risk prediction model among commercial pilots.

INTRODUCTION: It has been suggested that integrated cardiovascular risk management guidelines and absolute cardiovascular risk prediction scores should be used routinely in aeromedical risk assessment. In this study a cardiovascular disease (CVD) risk prediction model has been applied to UK commercial pilots as an occupational group. METHOD: This retrospective cross-sectional study measured the variables age, sex, body mass index (BMI), blood pressure, use of antihypertensive medication, current smoking, and diabetes status of commercial pilots. Individual 10-yr absolute CVD risk scores (also referred to as 10-yr global CVD risk) were calculated using a non-laboratory based Framingham Heart Study developed model. RESULTS: Of the 14,379 subjects eligible for the study, none had missing values for risk factors. None of the female pilots and 9.7% of all male pilots were found to be high risk. The mean 10-yr absolute CVD risk for the entire pilot population was 8.41% (median 5.6). High-risk pilots are concentrated around 60 yr of age, (mean 59, median 60 yr) with an age range of 40-81 yr. A sub-analysis of high-risk pilots younger than 65 revealed 1137 pilots in this group. CONCLUSION: The application of a 10-yr absolute CVD risk prediction model identified a group of pilots, previously unidentified, who may require a more comprehensive risk assessment. Pilots are continuing to fly commercially beyond the age of 60, which results in substantial increase in the CVD risk burden of the pilot population as a whole.

Reproductive history and adverse pregnancy outcomes in commercial flight crew and air traffic control officers in the United kingdom.

OBJECTIVE: To examine reproductive outcomes among flight crew. METHODS: Ten thousand two hundred five flight crew members and a control group of 2118 air traffic control officers completed a questionnaire in 2001 to 2004, United Kingdom. RESULTS: Similar proportions of flight crew and air traffic control officers reported having ever had difficulties in conceiving a baby. Risks of miscarriages and congenital malformations among pregnancies fathered by men who did not differ by occupation, but stillbirth risk was higher among flight crew (odds ratio = 2.85; 95% CI = 1.30-6.23). Among pregnancies reported by women, risks of miscarriage and stillbirth did not differ by occupation but risk of congenital malformations was higher among flight crew (odds ratio = 2.37; 95% CI = 0.43-13.06). CONCLUSIONS: Flight crew-related exposures were not associated with adverse reproductive outcomes except for possible links, based on small numbers, between paternal exposure and stillbirths and maternal exposure and congenital malformations.

Safety management as a foundation for evidence-based aeromedical standards and reporting of medical events.

The different interpretations by States (countries) of the aeromedical standards established by the International Civil Aviation Organization has resulted in a variety of approaches to the development of national aeromedical policy, and consequently a relative lack of harmonization. However, in many areas of aviation, safety management systems have been recently introduced and may represent a way forward. A safety management system can be defined as "A systematic approach to managing safety, including the necessary organizational structures, accountabilities, policies, and procedures" (1). There are four main areas where, by applying safety management principles, it may be possible to better use aeromedical data to enhance flight safety. These are: 1) adjustment of the periodicity and content of routine medical examinations to more accurately reflect aeromedical risk; 2) improvement in reporting and analysis of routine medical examination data; 3) improvement in reporting and analysis of in-flight medical events; and 4) support for improved reporting of relevant aeromedical events through the promotion of an appropriate culture by companies and regulatory authorities. This paper explores how the principles of safety management may be applied to aeromedical systems to improve their contribution to safety.

Increased circulating Dickkopf-1 in Paget's disease of bone.

UNLABELLED: Dickkopf-1 (Dkk-1) is a secreted inhibitor of Wnt signaling which in adults regulates bone turnover. Dkk-1 over-production is implicated in osteolytic disease where it inhibits bone formation and stimulates bone breakdown. Recently it was reported that osteoblastic cells from Paget's disease of bone (PDB) over-expressed Dkk-1. OBJECTIVE: To see if increased Dkk-1 was detected in serum from patients with PDB. RESULTS: Dkk-1 and total serum alkaline phosphatase activity (tsAP) were significantly elevated in sera from PDB patients. Patients with polyostotic PDB had significantly higher levels of tsAP but not Dkk-1, than monostotic patients. TsAP but not Dkk-1, was significantly lower in sera from bisphosphonate treated versus untreated PDB patients. Dkk-1 and tsAP were not significantly correlated. CONCLUSIONS: Dkk-1 may be a useful biomarker of PDB and we speculate that Dkk-1 may play a central role in the etiology of PDB.